As part of ongoing efforts to ensure patient protection in gene therapy trials, the Food and Drug Administration (FDA) and the National Institutes of Health (NIH) today announced two new initiatives to further strengthen the safeguards for individuals enrolled in clinical studies for gene therapy. These two new initiatives -- the Gene Therapy Clinical Trial Monitoring Plan and the Gene Transfer Safety Symposia -- complement and advance current patient protections.

FDA's clinical trials monitoring plan addresses emerging evidence that the monitoring by study sponsors of several recent gene therapy trials has been less than adequate. To buttress the rigor of the oversight, FDA will require that sponsors of gene therapy trials routinely submit their monitoring plans to the FDA.

FDA will review these monitoring plans and seek modifications as warranted to improve the quality of monitoring. FDA will also perform surveillance and "for cause" inspections of clinical trials to assess whether the plans are being followed and whether monitoring has been adequate to identify and correct critical problems. The sponsors will also have to address such issues as the experience and training of the monitors and the adequacy of the monitoring in their plans. In addition, NIH and FDA will seek to enhance the conduct of gene therapy trials by convening a conference of investigators at which the appropriate monitoring practices will be discussed by the most experienced professionals in the field.

Clinical trial monitoring is a powerful tool in enhancing the safety and protection of research subjects during a trial. Monitors are selected by and report to the sponsor or the sponsor's designee (e.g., a contract research organization). These monitors verify that the rights and well-being of human subjects are protected; that the conduct of the trial is in accordance with the protocol, regulatory requirements, and good clinical practices; and that data reporting (including safety reporting to IRB, FDA, and NIH) is accurate and complete.

In addition, in those instances where the gene therapy trial has an independent data and safety monitoring board (or equivalent) associated with it, the board's findings and recommendations regarding patient safety are shared with the IRB, FDA, and NIH. In some gene therapy trials, one or more of the investigators is also the sponsor or a member or employee of the sponsoring organization. NIH will work to develop procedures to further assure appropriately independent oversight of the conduct of such trials.

"Clinical trial monitoring and responsible reporting must be taken seriously by all parties involved in gene therapy trials," said Commissioner of Food and Drugs Jane E. Henney, M.D. "Our plan will help restore the confidence in the trials' integrity that is essential if gene therapy studies are to be able to fulfill their potential."

In a second new initiative, a series of Gene Transfer Safety Symposia, NIH and FDA will enhance patient safety by providing critical forums for the sharing and analysis of medical and scientific data from gene transfer research.

The symposia, which are expected to take place about four times a year, will bring together leading experts in gene transfer research and give them an opportunity to publicly discuss medical and scientific data germane to their specialties.

The first symposium will take place during this week's meeting of the Recombinant DNA Advisory Committee (RAC). Scientists and physicians will discuss the safety and future clinical applications of a new class of adenoviral vectors that have been extensively altered with the aim of improved safety.

Subsequent symposia will be held at the RAC, FDA's Biological Response Modifier Advisory Committee, and other venues. These symposia will address such gene transfer topics as monitoring of data safety; cardiovascular complications of vector administration; good clinical practice in research; cell and gene therapy guidance development for product quality control and assurance; entry criteria and informed consent for participants in gene transfer research; and use of drugs to control promoters in gene therapy vectors. Future symposia also will focus on topics such as the use of a particular vector, a specific disease for which gene transfer is an experimental therapeutic approach (such as hemophilia, Alzheimer's disease, or sickle cell disease) and/or a specific population of patients enrolled in gene transfer studies, such as newborns, children, the elderly, or normal volunteers.

To further increase their educational outreach efforts, FDA and NIH also will provide support for professional organizations and academic centers interested in holding safety conferences focused on gene therapy.

"The knowledge and understanding gained through these safety symposia and educational outreach efforts will guide the conduct of current trials and enhance the design of future gene transfer trials to maximize patient safety," said NIH Acting Director Ruth Kirschstein.

FDA also announced today that it is notifying all sponsors of gene therapy trials to supply additional information about cell banks, viral banks and other gene therapy products produced or generated in their facilities for potential use in non-clinical or clinical studies of human gene therapy. Among other gene therapy related information, FDA is asking the sponsors to provide quality control information for each lot of products produced in their facilities or used in their clinical trials.

Today's initiatives are part of the Administration's ongoing efforts to ensure the safety of patients enrolled in gene therapy clinical trials. Last month, President Clinton asked Health and Human Services Secretary Donna E. Shalala to instruct FDA and NIH to accelerate their review of gene therapy guidelines and regulations. Specifically, the President asked how information can be better shared with the public and whether requirements on informed consent need to be strengthened.

In the past few months, FDA and NIH have taken individual and cooperative actions to achieve greater adherence by researchers to existing requirements and guidance and to bolster the protection of study participants and the integrity of gene therapy trials. These include:

The NIH will undertake a series of "not for cause" site visits to NIH-funded institutions to review institutional understanding of, and compliance with, a range of NIH rules, regulations, and guidelines, including the NIH Guidelines and policies relevant to gene transfer research, conflict of interest, and invention reporting.

NIH directed all institutions conducting human gene transfer research to review their institutional policies and procedures to ensure compliance with the NIH Guidelines. NIH is also contacting every clinical gene transfer investigator to ensure that they have submitted all serious adverse events to the NIH, including serious adverse events from trials that are no longer active.

A working group reporting to the NIH Director was established to comprehensively review in public session the role of the NIH in gene therapy clinical trial oversight.

A subcommittee of the RAC is examining the reporting, analysis and public disclosure of serious adverse events to the NIH, with the aim of recommending changes in the NIH Guidelines.

FDA will conduct more inspections to increase oversight of Investigational New Drug applications in gene therapy.

NIH is completing the development of an interactive web-based database to provide public access to data on gene transfer research, which will be online by October 2000.

FDA plans to issue a proposed rule on the public disclosure of information regarding gene therapy clinical trials that would provide more information on these trials to the general public.

FDA is enhancing regulatory research to improve product safety.

FDA has provided guidance documents to industry and other interested parties on gene therapy products and will take action to build upon existing guidance.